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While Cobicistat and Fortovase are known as HIV drugs, Iopromide is a contrast agent and Cangrelor is an anti-platelet drug. Furthermore, molecular dynamic (MD) simulations using GROMACS were performed to calculate the stability of the top-ranked compounds in the active site of Mpro. After extensive computational studies, we propose that Cobicistat and Hopeaphenol show potential to be excellent drugs that can form the basis of treating COVID-19 disease. Communicated by Ramaswamy H. Sarma.A new pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and become pandemic with thousands new deaths and infected cases globally. To treat the patients with coronavirus disease (COVID-19), currently no effective drug or vaccine is available. This necessity motivated us to explore potential lead compounds based natural products targeting main protease (Mpro) enzyme of SARS-CoV-2. The Mpro enzyme plays a key role in mediating viral replication and transcription and thus being considered as an attractive drug target. Herein, comprehensive computational investigations were performed to identify new lead compounds against main protease enzyme. In this study, the candidate anthocyanin-derived compounds from PubChem database were filtered considering antiviral characteristics of anthocyanins. The structure-based pharmacophore modeling was developed based on the co-crystallized structure of the enzyme with its biological active inhibitor. The generated hypotheses were applied for virtual screening-based PHASE Screen Score. Docking based virtual screening work flow was used to generate hit compounds using HTVS, SP and XP based Glide Gscore. The obtained hit compounds were filtered using ADMET pharmacological and physicochemical properties screening. Molecular dynamics simulations were performed to explore the binding affinities of the considered compounds. Our study identified six best anthocyanin-derived natural compounds which could be used as promising lead compounds against main protease SARS-CoV-2 virus. Communicated by Ramaswamy H. Sarma.With ageing mental health issues, as age-related cognitive decline, increase. This study aims to evaluate the prevalence of cognitive impairment among older European adults and to evaluate its association with clinical and sociodemographic variables, using SHARE. Numeracy, temporal orientation, verbal fluency, and memory were the measures used to evaluate cognitive performance. From 44 963 individuals included, mean age was 70.0±9.0 years old and 56.3% were female. Overall prevalence of impairment was of 13.0% (temporal orientation), 24.8% (numeracy), 27.6% (verbal fluency) and 50.5% (memory). Men showed higher impairment prevalence in temporal orientation and memory and lower in numeracy and verbal fluency. Age, fewer years of education, difficulties performing iADLs, physical inactivity, and poor self-perceived health were independently associated with impairment in all cognitive abilities. These results showed the burden of cognitive impairment across Europe. Factors identified as associated should be taken in consideration to develop effective interventions to prevent cognitive decline.

Endovascular therapy using balloon expandable stents has become the treatment standard for most iliac atherosclerotic lesions. We aimed to assess the safety and performance of the Dynamic stainless-steel balloon-expanding stent system in this location.

BIODYNAMIC is a retrospective single center study including consecutive patients with iliac lesions treated with the Dynamic stent system. Not included were implantations inside an endograft. The primary endpoint was freedom from major adverse limb events (MALE) at 12 months, defined as index limb amputation or target lesion revascularization (TLR). Secondary endpoints were procedure success, ankle brachial index (ABI) and Rutherford class change, mortality and freedom from TLR after 12 months.

Within two years, 182 patients with 234 lesions in the common iliac artery were enrolled. Rutherford class 5 and 6 were present in 11.5% of patients, average stent diameter was 8.0 ± 0.5 mm and stented length 40.0 ± 15.3 mm. The primary endpoint was reached in 96.2% (225/234) of the cases, with six TLR (2.6%) and three target limb amputations (1.3%). Procedure success was obtained in all but three patients (98.4%). In paired analysis, ABI improved by 0.25 ± 0.21 from baseline to 0.90 ± 0.16 post-procedure and Rutherford class improved by -1.75 ± 1.53. There were four non-device-related deaths (2.2%). Freedom from TLR was 97%, 95.3%, 94% and 92.7% at 24, 36, 48 and 60 months, respectively.

The Dynamic balloon-expandable stent system proved to be safe and effective in a population with common iliac artery lesions.

The Dynamic balloon-expandable stent system proved to be safe and effective in a population with common iliac artery lesions.This paper examines the continuing role of consultants within the profession of chemistry in the late nineteenth and twentieth centuries. Consultants were a prominent part of the profession in the late nineteenth century, but were overtaken in numerical terms by chemists working in academia, government and industry in the first half of the twentieth century. The paper demonstrates, however, that numbers later stabilised and then goes on to examine the characteristics of those chemists who worked as consultants as compared to the wider chemical community. It argues that the survival of consultancy is best explained in terms of a number of differing models of consultancy work. Whilst for some chemists, consultancy was their main occupation, for others it was a phase in their careers or a secondary occupation alongside another post. The continuing value of consultancy work was related to its very versatility.G protein-coupled receptors (GPCRs), a large superfamily of transmembrane (TM) proteins, allosterically transduce the signal of ligand binding in the extracellular (EC) domain to couple to effector proteins in the intracellular (IC) domain, therefore forming the largest class of drug targets. The A2A adenosine receptor (A2AAR), a class-A GPCR, has been extensively studied as it offers numerous possibilities for therapeutic applications. However, the mechanism of allosteric communication between EC and IC domains is not completely clear. selleck kinase inhibitor In this work, we utilize torsional mutual information to quantify the correlated motions of residue pairs from its molecular dynamics (MD) simulation trajectories, and further use the complex network model to obtain allosteric pipelines and hubs. The identified allosteric communication pipelines mainly transmit the signal from EC domain to the cytoplasmic ends of TM helix 5 (TM5), TM6 and TM7. The allosteric hubs, mostly located at TM5, TM6 and TM7, play an important role in mediating allosteric signal transmission to keep the receptor rigid and prevent G protein from binding to IC domain, which can explain the reason why their mutations distant from ligand-binding site do not affect the ligand binding affinity but affect the ligand efficacy.